Process for producing 2-thia substituted 1,4 diones

ABSTRACT

Process for producing 3-thia substituted alkane 1,4 diones comprising the steps of:

This application is a continuation-in-part of co-pending application forU.S. Pat. No. 386,452 filed on Aug. 7, 1973 now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to novel processes for producing 3-thiasubstituted alkane 1,4-diones.

Artifical flavoring agents for foodstuffs have received increasingattention in recent years. In many areas, such food flavoring agents arepreferred over natural flavoring agents at least in part because of theuniform flavor that may be so obtained. For example, natural foodflavoring agents such as extracts, essences, concentrates and the likeare often subject to wide variation due to changes in the quality, typeand treatment of the raw materials. Such variation can be reflected inthe end product and results in unreliable flavor characteristics anduncertainity as to consumer acceptance and cost. Additionally, thepresence of the natural product in the ultimate food may be undesirablebecause of increased tendency to spoil. This is particularly troublesomein convenience and snack food usage where such products as dips, soups,chips, prepared dinners, canned foods, sauces, gravies and the like areapt to be stored by the consumer for some time prior to use.

The fundamental problem in preparing artificial flavoring agents is thatof achieving as nearly as possible a true flavor reproduction. Thisgenerally proves to be a difficult task since the magnetism for flavordevelopment in many foods is not understood. This is noteable inproducts having meaty and roasted flavor characteristics. It is alsonoteable in products having vegetable-like and hydrolyzed vegetableprotein-like and anise-like flavor characteristics.

Reproduction of roasted and meat flavors and aromas and vegetable-likeand hydrolyzed vegetable protein-like and anise-like flavors and aromashas been the subject of the long and continuing search by those engagedin the production of foodstuffs. The severe shortage of foods,especially protein foods, in many parts of the world has given rise tothe need for utilizing non-meat sources of proteins and making suchproteins as palatable and as meatlike as possible. Hence, materialswhich will closely simulate or exactly reproduce the flavor and aroma ofroasted meat products and liver products and vegetable products arerequired.

Moreover, there are a great many meat containing or meat based foodspresently distributed in a preserved form. Examples being condensedsoups, dry-soup mixes, dry meat, freeze-dried or lyophilized meats,packaged gravies and the like. While these products contain meat or meatextracts, the fragrance, taste and other organoleptic factors are veryoften impaired by the processing operation and it is desirable tosupplement or enhance the flavors of these preserved foods withversatile materials which have either roasted meat or gravy-like orvegetable-like or meat-like or ham-like nuances.

2-Alkylfuran-3-thiols and bis (alkyl-3-furyl) disulfides are disclosedin U.S. Pat. No. 3,723,475 issued on Mar. 27, 1973 to supply meatyflavor aroma and taste nuances to foodstuffs. 2- thiasubstituted-1,4-diones are disclosed in U.S. Pat. No. 3,836,563 issuedon Sept. 17, 1974 to also supply meaty flavors to foodstuffs.

Swiss Pat. No. 531,313 discloses the addition of hydrogen sulfide acrossa double bond, eliminating the double bond.

Such a reaction, however, is not shown in conjunction with a chemicalcompound which has two ketone moieties.

The mechanism of the addition of hydrogen sulfide across a double bondof an alpha-beta-unsaturated ketone is set forth at lines 40-67 ofcolumns 3 and 4 of Swiss Pat. No. 531,559. The formation of thio estersusing thio acetic acid and unsaturated ketones is set forth at lines15-20 of column 6 of Swiss Pat. No. 531,559.

U.S. Pat. No. 2,630,452 to Crouch, et al discloses processes forreacting unsaturated nitriles with thio acids whereby the thio estermoiety adds to the double bond at the "alpha" position with respect tothe CN moiety using an aqueous alkali metal hydroxide catalyst or aquaternary ammonium compound catalyst. The substance of Crouch, et almay be illustrated by the following reaction betweeen acrylonitrile andthioacetic acid: ##EQU1## At column 2, lines 40-45, Crouch, et alstates:

"In accomplishing the thioacetic acidacrylonitrile reaction, it has beenfound to be highly advantageous to employ certain basic catalysts asreaction promoters and directors. The preferred catalyst is a quaternaryammonium compound designated by the general formula . . . "

In Example IV of Crouch, et al, acrylonitrile is reacted with thioaceticacid in the presence of a t-butyl hydroperoxide catalyst at atemperature of 43°-49°C.

U.S. Pat. No. 3,441,589 to Oswald discloses reaction of thiol compoundssuch as mercaptans and thiolcarboxylic acids being selectively added toesters which, in turn, are formed by the reaction of maleic acid,fumaric acid or maleic anhydride with terminally unsaturated alcoholssuch as allyl alcohol at either of the terminal double bonds of theester functionality or at the maleic or fumaric side of unsaturationwith the use of either free radical or ionic catalysts. At column 7,Example 8, Oswald teaches the reaction of diallyl maleate withthiolacetic acid to form n-(3-acetylthio)-propyl allyl maleate accordingto the following reaction: ##SPC3##

in the presence of a free radical catalyst, such as ultraviolet or gammaradiation or a "wide variety of peroxidic and azo compounds" (see column3, lines 60-62).

Reid "Organic Chemistry of Bivalent Sulfur", Volume IV, 1962, ChemicalPublishing Co., Inc.; discloses reactions of thioacetic acid withunsaturated compounds. At pages 15 and 16 Reid states:

"The most interesting reaction of thioacetic acid is its ready additionto unsaturates. An example of this is its addition to acrylonitrile. Inthis it exhibits its mercaptan character but in activity it farsurpasses most mercaptans. Usually the addition takes placespontaneously and completely. With styrene the reaction is: ##SPC4##

The product is the beta-phenethyl ester of thioacetic acid and isidentical with that from phenethyl mercaptan and acetyl chloride . . . "

No teaching exists in the prior art to show that where R₂ is lower alkyland R₁ is hydrogen, the effect of carrying out a reaction of a2-ene-4-one-1-al with a thioacid (in the presence of base) is directiveleading substantially to a reaction product where the thioestersubstitution is alpha to the ketone moiety and not the aldehyde moiety.

Furthermore, given the 2-ene-1,4-dione reactants of our invention, thereis no prediction in the prior art that either (i) no catalyst isnecessary in the case of using a hex-3-ene-2,5-dione reactant, or (ii) abasic catalyst is needed and the addition is directive in the case ofusing a pent-2-ene-4-one-1-al.

The processes of the present invention provide straightforward methodsfor producing 3-thia substituted alkane 1,4 diones in good yields in aneconomical manner.

Briefly, the processes of our invention comprise the steps of:

i. Providing a 2-ene-alkane 1,4 dione having the structure: ##SPC5##

ii. Intimately admixing said 2-ene-alkane-1,4 dione with a sulfurcompound having the formula:

    R.sub.3 SH

thereby providing a substituted or unsubstituted 2-thia substituted 1,4dione having the structure: ##SPC6##

wherein

R₃ is selected from the group consisting of acyl and aroyl, wherein R₂is lower alkyl; and wherein R₁, R₄ and R₆ are the same or different andare each selected from the group consisting of hydrogen and lower alkyl;wherein when R₁ is hydrogen, the reaction is carried out in the presenceof an organic base; and wherein when R₁ is lower alkyl, the reaction iscarried out in the absence of catalyst.

Two particularly novel features of our invention involve (i) addition ofthe thiol acids, either ##EQU2## or ##EQU3## to a hex-3-ene-2,5-dione,e.g., having the structure: ##SPC7##

at room temperature in the absence of any catalyst to produce economicyields of 3-thia substituted alkane 1,4 dione, e.g., having thestructure: ##SPC8##

and (ii) addition of a thiol acid, either ##EQU4## or ##EQU5## topent-3-ene-4-one-1-als, e.g., having the structure: ##SPC9##

in the presence of an organic base to yield a 3-thia substitutedpentane-4-one-1-al, e.g., having the structure: ##SPC10##

the addition being directive to that carbon atom (originally having theC=C double bond) which is "alpha" to the carbonyl group of the ketonemoiety rather than the aldehyde moiety.

Examples of thio acids useful in our process are:

thioacetic acid

thiopropionic acid

thiobutyric acid

thioisobutyric acid

thio-n-pentenoic acid

thiocinnamic acid

thiobenzoic acid

2-methyl-thiobenzoic acid

3-methyl-thiobenzoic acid

4-methyl-thiobenzoic acid

2,4-dimethyl-thiobenzoic acid

3,5-dimethyl-thiobenzoic acid

Whether an organic base is used or not in the reaction with the2-ene-1,4 dione with the thio acid having the formula R₃ SH, the2-ene-1,4 dione can be exemplified as follows:Compound R₁ R₂R₄Name______________________________________3-Hexen-2,5-dione MethylMethyl Hydrogen3-Methyl-3-hexen- Methyl Methyl Methyl2,5dione3-Methyl-3-hepten- Methyl Ethyl Methyl2,5 dione3-Ethyl-3-hepten-Methyl Ethyl Ethyl2,5-dione4-Ethyl-4-octen- Ethyl Ethyl Ethyl3,6dione3-Propyl-3-hepten- Methyl Ethyl Propyl2,5 dione4-Methyl-3-hepten-Ethyl Methyl Methyl2,5 dione4-Methyl-4-octen- Ethyl EthylMethyl3,6-dione4-Methyl-4-nonen- Ethyl PropylMethyl3,6-dione4-Propyl-3-hepten- Ethyl MethylPropyl3,6-dione5-Methyl-5-decen- Propyl PropylMethyl4,7-dione5-Methyl-4-nonen- Propyl EthylMethyl3,6-dione4-Methyl-3-nonen- Butyl MethylMethyl2,5-dione4-Ethyl-3-nonen- Butyl MethylEthyl2,5-dione3-Methyl-3-nonen- Methyl ButylMethyl2,5-dione3-Propyl-3-nonen- Methyl Butyl Propyl2,5dione3-Butyl-3-hexen- Methyl Methyl Butyl2,5-dione4-Octen-3,6-dioneEthyl Ethyl Hydrogen______________________________________

As stated above, R₁ and R₂ can each be hydrogen for the purposes ofthese processes of our invention in the event that in the reaction ofthe 2-ene-1,4 dione with the thioacid of the formula R₃ SH, an organicbase is used. Hence, in addition to the foregoing compounds, thefollowing compounds can be utilized in the reaction with R₃ SH:

    Compound        R.sub.1  R.sub.2  R.sub.4                                     Name                                                                          ______________________________________                                        2-Buten-1,4-dial                                                                              Hydrogen Hydrogen Hydrogen                                    2-Methyl-2-buten-                                                                             Hydrogen Hydrogen Methyl                                      1,4-dial                                                                      2-Pentenal-4-one                                                                              Methyl   Hydrogen Hydrogen                                    2-Hexenal-4-one Ethyl    Hydrogen Hydrogen                                    3-Methyl-2-hexenal                                                                            Ethyl    Hydrogen Methyl                                      4-one                                                                         2-Methyl-2-pentenal                                                                           Hydrogen Hydrogen Methyl                                      4-one                                                                         2-Methyl-2-heptenal                                                                           Hydrogen Propyl   Methyl                                      4-one                                                                         2-Methyl-2-octenal                                                                            Hydrogen Butyl    Methyl                                      4-one                                                                         ______________________________________                                    

Examples of useful organic bases are piperidine, pyridine, quinoline,triethyl amine and alpha-picoline.

The reaction may be carried out in a solvent such as water or an ethersuch as diethyl ether or a hydrocarbon such as benzene or hexane orcyclohexane. The reaction may also be carried out without the use of asolvent. The reaction may be carried out under reflux conditionsalthough temperatures varying from 0° up to 60°C are suitable and willgive rise to commercially suitable yields. When the reaction is carriedout with highly volatile reactants, higher pressures than atmosphericpressure are preferred, e.g., three atmospheres pressure. Examples ofreaction products, 3-thia-substituted-1,4-diones which are formed fromthe reaction of the 2-ene-1,4-diones with the thioacids, having theformula R₃ SH are as follows:

                              3-Thia Substituted                                  2-ene-1,4 dione                                                                            R.sub.3 SH   1,4-dione Reaction                                  Reactant     Reactant     Product                                             ______________________________________                                        3-Hexen-2,5-dione                                                                          Thioacetic acid                                                                            3-Thioacetyl-                                                                 2,5-hexan-dione                                     3-Methyl-3-hexen-                                                                          Thiopropionic                                                                              3-Thiopropionyl-4-                                  2,5-dione    acid         methyl hexan-2,5-                                                             dione                                               3-Methyl-3-hepten-                                                                         Thiobenzoic acid                                                                           4-Thiobenzoyl-4-                                    2,5-dione                 methyl heptan-3,6-                                                            dione                                               4-Ethyl-4-octen-                                                                           Thioacetic acid                                                                            4-Thioacetyl-5-                                     3,6-dione                 ethyl-octan-3,6-                                                              dione                                               2-Buten-1,4-dial                                                                           Thioacetic acid                                                                            2-Thioacetyl-butan-                                                           1,4-dial                                            2-Pentenal-4-one                                                                           4-Methyl-thio                                                                              3-Thiobenzoyl-                                                   benzoic acid pentenal-4-one                                      2-Pentenal-4-one                                                                           Thioacetic acid                                                                            3-Thioacetyl-                                                                 pentenal-4-one                                      ______________________________________                                    

The 2-thia substituted-1,4-diones as exemplified above are useful foraltering the organoleptic properties of consumable materials, moreparticularly, foodstuffs. Thus, for example,3-thioacetyl-2,5-hexanedione has a roasted meat aroma and a pot-roastand roasted meat flavor tested at levels of 5 ppm. Its flavor thresholdvalue is at 1 ppm. The compound 3-thiobenzoyl-2,5-hexanedione has aberry and a meat aroma, an allium, earthy and horseradish flavor atconcentrations of approximately 0.5 ppm. Its threshold value is at 0.5ppm. 3-Thiobenzoyl-2,5-hexanedione at 5 ppm evaluated in beef bouillonhas a meaty note. 3-Thioacetyl-2,5-hexanedione at 5 ppm adds a burntmeat note to beef bouillon. 3-Thiobenzoyl-2,5-hexanedione adds a slightgreen chicken meat note to chicken broth at 2.5 ppm.3-Thioacetyl-2,5-hexanedione adds eggy chicken notes to chicken broth at2.5 ppm.

The products of the process of our invention may be used as reactionintermediates and, when used as such, the thia-substituted 1,4-dionesproduced by the process of our invention are then cyclized to formsubstituted or unsubstituted 3-thiafurans according to the followingreaction: ##SPC11##

wherein R₁ and R₂ are the same or different and are each hydrogen orlower alkyl; wherein R₃ is either acyl or aroyl and R₄ is hydrogen orlower alkyl. The resulting 3-thiafurans may be used as such for theirorganoleptic properties or they may be hydrolyzed and then reacylated oraroylated to form other acyl thia or aroyl thia substituted furans whichhave still other organoleptic properties useful for flavoringfoodstuffs.

The compound having the structure: ##SPC12##

may also be intermediates in that they may be hydrolyzed first using aweak base (e.g., 2-5% aqueous NaOH, LiOH or KOH) and then neutralizingwith acid to a pH of 5-6 to form compounds having the structure:##SPC13##

which have useful organoleptic properties. Thus, for example,3-thioacetyl-2,5-hexanedione is hydrolyzed to 3-mercapto-2,5-hexanedioneby treating the 3-thioacetyl compound first with 2% aqueous NaOH andthen adjusting the pH to about 5 using 10% HCl. Hydrolysis conditionsare preferably atmospheric pressure and 20°-50°C with ambienttemperature being most convenient and economical.

The 3-thia alkane-1,4 dione derivatives and mixtures thereof producedaccording to the present invention can be used to alter, vary, fortify,modify, enhance, or otherwise improve the organoleptic properties,including flavor and/or aroma of a wide variety of materials which areingested, consumed, or otherwise organoleptically sensed. The term"alter" in its various forms will be understood herein to mean thesupplying or imparting a flavor character or note to an otherwise bland,relatively tasteless substance, or augmenting an existing flavorcharacteristic where the natural flavor is deficient in some regard, orsupplementing the existing flavor or aroma impression to modify theorganoleptic character. The materials which are so altered are generallyreferred to herein as consumable materials.

Such 3-thia alkane-1,4-dione derivatives are accordingly useful inflavoring compositions. Flavoring compositions are herein taken to meanthose which contribute a part of the overall flavor impression bysupplementing or fortifying a natural or artificial flavor in amaterial, as well as those which supply substantially all the flavorand/or aroma character to a consumable article.

The term "foodstuff" as used herein includes both solid and liquidingestible materials for man or animals, which materials usually do, butneed not, have nutritional value. Thus, foodstuffs includes meats,gravies, soups, convenience foods, malt and other alcoholic ornon-alcoholic beverages, milk and dairy products, nut butters such aspeanut butter and other spreads, seafoods, including fish, crustaceans,mollusks, and the like, candies, breakfast foods, baked goods,vegetables, cereals, soft drinks, snack foods, dog and cat foods, otherveterinary products, and the like.

When the 3-thia alkane-1,4 dione derivatives produced according to theprocess of this invention are used in a food flavoring composition, theycan be combined with conventional flavoring materials or adjuvants. Suchco-ingredients or flavoring adjuvants are well known in the art for suchuse and have been extensively described in the literature. Apart fromthe requirement that any such adjuvant material be ingestiblyacceptable, and thus non-toxic or otherwise non-deleterious,conventional materials can be used and broadly include other flavormaterials, vehicles, stabilizers, thickeners, surface active agents,conditioners, and flavor intensifiers.

Examples of preferred co-flavoring adjuvants are:

Methyl thiazole alcohol (4-methyl-5-betahydroxyethyl thiazole);

2-Methyl butanethiol;

4-Mercapto-2-butanone;

3-Mercapto-4-pentanone;

1-Mercapto-2-propanone;

Benzaldehyde;

Furfural;

Furfural alcohol;

2-Mercapto propionic acid;

2-Pentene;

Alkyl pyrazine;

Methyl pyrazine;

2-Ethyl-3-methyl pyrazine;

Tetramethyl pyrazine;

Polysulfides;

Dipropyl disulfide;

Methyl benzyl disulfide;

Alkyl thiophenes;

2-Butyl thiophene;

2,3-Dimethyl thiophene;

5-Methyl furfural;

Acetyl furan;

2,4-Decadienal;

Guiacol;

Phenyl acetaldehyde;

δ-Decalactone;

d-Limonene;

Acetoin;

Amyl acetate;

Maltol;

Ethyl butyrate;

Levulinic acid;

Piperonal;

Ethyl acetate;

n-Octanal;

n-Pentanal;

Hexanal;

Diacetyl;

Monosodium glutamate;

Sulfur-containing amino acids;

Cysteine;

Hydrolyzed vegetable protein;

Hydrolyzed fish protein; and

Tetramethyl pyrazine

The 3-thia alkane-1,4 dione derivatives, or the compositionsincorporating them, as mentioned above, can be combined with one or morevehicles, or carriers for adding them to the particular product.Vehicles can be edible or otherwise suitable materials such as ethylalcohol, propylene glycol, water, and the like. Carriers includematerials such as gum arabic, carrageenan, other gums, and the like. The3-thia alkane-1,4 dione compounds according to this invention can beincorporated with the carriers by conventional means such asspray-drying, drum-drying, and the like. Such carriers can also includematerials for coacervating the 3-thia alkane-1,4 dione derivatives (andother flavoring ingredients, as present) to provide encapsulatedproducts. When the carrier is an emulsion, the flavoring composition canalso contain emulsifiers such as mono- and diglycerides of fatty acidsand the like. With these carriers or vehicles, the desired physical formof the composition can be prepared.

The quantity of 3-thia alkane-1,4 dione derivatives or mixtures thereofutilized should be sufficient to impart the desired flavorcharacteristic to the product, but on the other hand, the use of anexcessive amount of the derivative is not only wasteful anduneconomical, but in some instances too large a quantity may unbalancethe flavor or other organoleptic properties of the product comsumed. Thequantity used will vary depending upon the ultimate foodstuff; theamount and type of flavor initially present in the foodstuff; thefurther process of treatment steps to which the foodstuff will besubjected; regional and other preference factors; the type of storage,if any, to which the product will be subjected, and the preconsumptiontreatment, such as baking, frying, and so on, given to the product bythe ultimate consumer. Accordingly, the terminology "effective amount"and "sufficient amount" is understood in the context of the presentinvention to be quantitiatively adequate to alter the flavor of thefoodstuff.

It is accordingly preferred that the ultimate compositions contain fromabout 0.02 parts per million (ppm) to about 250 ppm of 3-thia-alkane-1,4dione derivative or derivatives. More particularly, in food compositionsit is desirable to use from 0.05 ppm to 100 ppm for enhancing flavorsand in certain preferred embodiments of the invention, from about 0.2 to50 ppm of the derivatives are included to add positive flavors to thefinished product. All parts, proportions, percentages, and ratios hereinare by weight unless otherwise indicated.

The amount of 3-thia alkane-1,4 dione material or materials of ourinvention to be utilized in flavoring compositions can be varied over awide range depending upon the particular quality to be added to thefoodstuff. Thus, amounts of one or more derivatives according to thepresent invention of from about 2 ppm up to 80 or 90 percent of thetotal flavoring composition can be incorporated in such compositions. Itis generally found to be desirable to include from about 10 ppm up toabout 0.1 percent of the 3-thia alkane-1,4 dione derivatives in suchcompositions.

The following examples I, II, V, VI, VII and X are given to illustrateembodiments of the invention as it is preferably preferred to practiceit. Examples III, IV, VIII and IX are given to illustrate the usefulnessof the products produced by the process of our invention. It will beunderstood that these examples are illustrative and the invention is notto be considered as restricted thereto except as indicated in theappended claims.

EXAMPLE I (PREPARATION OF CIS-3-HEXENE-2,5-DIONE)

In a 1000 ml round bottom flask fitted with condenser and magneticstirrer are placed 200 g of 2,5-dimethoxy-2,5-dimethyl-2,5-dihydrofuranand 200 ml of a 1% aqueous acetic acid solution. The resulting solutionis heated to reflux, refluxed for 2 minutes, cooled with an ice bath to25°C and 625 ml of a 2% sodium bicarbonate solution is added. Thesolution is saturated by addition of 23 g of sodium chloride andextracted with methylene chloride (1 × 200 ml and 3 × 100 ml). Afterdrying over sodium sulfate removal of the methylene chloride in vacuogives 142 g of crude cis-3-hexene-2,5-dione which by GLC analysis isabout 90% product having the structure: ##SPC14##

EXAMPLE II (PREPARATION OF 3-THIOACETYL-2,5-HEXANEDIONE)

In a 1000 ml round bottom flask fitted with magnetic stirrer,thermometer, addition funnel and reflux condenser are placed 142 g ofcrude cis-3-hexene-2,5-dione (ex Example I), 380 ml of ether and 5 dropsof piperidine. Thio acetic acid (96.6 g) is added over a period of onehour. When about 1/8 of the thio acetic acid is added, the solutionbegins to reflux which continues during the remainder of the addition.After addition is complete, the mixture is allowed to stand for 85minutes. Ether is then removed in vacuo (water asperator) to give 235 gof crude material containing about 91% 3-thioacetyl-2,5-hexanedione.Distillation of a 134 g portion of the crude gives 84.5 g of3-thioacetyl-2,5-hexanedione boiling at 86° to 87°C at 0.5 torr. NMR, IRand mass spectral analyses confirm the structure: ##SPC15##

EXAMPLE III (PREPARATION OF 3-PROPYLTHIO-2,5-HEXANEDIONE)

In a 500 ml flask fitted with thermometer, addition funnel, refluxcondenser and magnetic stirrer are placed 95 ml of ether, 35.4 g ofcis-3-hexene-2,5-dione and one drop of piperidine. Addition of 24 g ofn-propanethiol is started and as the addition progresses more piperidineis added (33 drops total) periodically. After standing 18 hours, thesolution is washed successively with two 7.5 ml portions of 10%hydrochloric acid, saturated sodium chloride solution (10 ml), 5% sodiumbicarbonate solution and two 10 ml portions of saturated sodium chloridesolution. The ether solution is dried over sodium sulfate andconcentrated to give 51.4 g of a dark yellow oil. Analysis by GLC showsthe material to be essentially pure 3-thiopropyl-2,5-hexanedione. Massspectral analysis shows molecular ion 188 then descending order 43, 103,41, 145, 71, 114 and 61 m/e units.

EXAMPLE IV (PREPARATION OF 3-MERCAPTO-2,5-HEXANEDIONE)

To 150 ml of a 2% sodium hydroxide solution in a flask fitted forstirring is added 10 g of 3-thioacetyl-2,5-hexanedione. After stirringfor one hour the pH of the mixture is adjusted to 5-6 by the addition ofdilute (10%) hydrochloric acid, the solution is saturated with sodiumchloride solution and extracted with ether (4 × 25 ml). The etherextracts are combined, washed with saturated sodium chloride solution(15 ml), dried and concentrated in vacuo to give 6.2 g of crude3-mercapto-2,5-hexanedione. Vacuum distillation gives 2.5 g of3-mercapto-2,5-hexanedione boiling at 57°-59°C at 0.85 torr. NMR, IR andmass spectral analyses confirm the structure as3-mercapto-2,5-hexanedione.

EXAMPLE V (PREPARATION OF 2-THIOACETYL-1,4-BUTANE-DIAL) A. Preparationof 2-butene-1,4-dial

A mixture of 2,5-dimethoxy-2,5-dihydrofuran (20 g), water (80 ml) andacetic acid (3 drops) is stirred for 105 minutes at room temperature, 22minutes at 40°C and 90 minutes between 60°C and 75°C. GLC analysis atthis point indicates 15.7% starting material and 83.5%2-butene-1,4-dial. The mixture is cooled to 25°C and sodium bicarbonate(0.3 g) is added.

B. Preparation of 3-thioacetyl-1,4-butanedial

To the aqueous solution obtained in Section A supra, is added 10 g ofthio acetic acid during a 14 minute period. During the addition, thetemperature is kept below 30°C by intermittent application of a coolingbath. After 110 minutes, the reaction mixture is extracted withmethylene chloride (3 × 35 ml). The combined methylene chloride extractsare dried and then concentrated in vacuo to give 17.8 g of yellow oilcontaining about 80% 2-thioacetyl-1,4-butanedial. The compound isidentified through mass spectral, NMR and IR analyses as having thestructure: ##SPC16##

M.S. - No molecular ion; remaining peaks in decreasing

intensity - 43, 29, 27, 45, 55, 60, 84, 100

and 142 m/e units.

NMR (CDCl₃) 2.38 (s,3) 3.02 (multiplet 2,J=10H_(z)),

4.46 (r,1J=10H^(z)) 9.40 (s,1) and

9.68 (s,1) ppm.

IR (thin film) - 2850, 2750, 1720, 1700 (shoulder),

1388, 1352, 1132 and 958 cm.sup.⁻¹.

EXAMPLE VI (PREPARATION OF 3-THIOACETYL-4-OXO-PENTANAL) A.4-oxo-2-pentenal

Into a 5 liter, three-necked flask fitted with mechanical stirrer,thermometer and vacuum take-off are placed 600 g of2-methyl-2,5-dimethoxy-2,5-dihydrofuran and 2400 ml of deionized water.After 20 minutes of stirring at room temperature, the mixture becomeshomogeneous and has a pale yellow green color. Analysis of a sample ofthe reaction mixture by GLC after 3.25 hours shows 22% methanol, 67%4-oxo-2-pentenal and 9% starting material. Vacuum (26 torr.) is appliedto the reaction mixture while maintaining the temperature of thereaction mixture between 25° and 30°C. After 3.25 hours GLC analysisshows 13% methanol, 82% 4-oxo-2-pentenal and 3.2% starting material. Thevacuum is removed and the reaction mixture is allowed to stand at roomtemperature overnight. Analysis after standing overnight shows 12.9%methanol, 85% 4-oxo-2-pentenal and 2.1% starting material.

B. 3-thioacetyl-4-oxo-pentanal

In a 5 liter, three-necked flask fitted with mechanical stirrer,thermometer and addition funnel are placed 2325 ml of the solutionobtained in (A) and 2 ml of piperidine diluted in 5 ml of water. To thissolution is added a mixture of thio acetic acid (292.3 g) and piperidine(13 ml) over a 20 minute period. After standing an additional 10minutes, 20 ml of concentrated hydrochloric acid is added, the resultingmixture poured into a separatory funnel and the oil layer removed. Theaqueous layer is extracted with benzene (500 ml) and methylene chloride(2 × 500 ml). The benzene extract is combined with the oil layer and themixture is dried over sodium sulfate. The methylene chloride extractsare combined and dried over sodium sulfate. Solvent removal in vacuo(40°-45°C both at 15 torr.) gives 414.5 g of crude oil from the benzeneextract and 172.5 g of crude oil from the methylene chloride extracts.The crude oil is distilled under vacuum to give3-thioacetyl-4-oxo-pentanal boiling at 94°-98°C at 0.3-0.55 mm Hg.

EXAMPLE VII (PREPARATION OF 3-THIOBENZOYL-2,5-HEXANEDIONE)

In a 50 ml three-necked flask equipped with thermometer, 10 ml additionfunnel and magnetic stirrer is placed 6 g of2,5-dimethoxy-2,5-dimethyl-2,5-dihydrofuran, 24 ml H₂ O and 1 drop ofglacial acetic acid. The mixture (which is crude cis-3-hexene-2,5-dione)is stirred for one hour until homogeneous. Then 5.25 g thiobenzoic acidis added over a five-minute period. The mixture is allowed to stand foreighteen more minutes and is then extracted with 35 ml of methylenechloride. After drying over anhydrous sodium sulfate and subsequentsolvent removal, 7.55 g of crude 3-thiobenzoyl-2,5-hexanedione isrecovered. The crude material is purified by column chromatography on108 g silicic acid packed in ether:hexane (1:9) mixture. Elution with630 ml ether:hexane (1:9) solvent mixture; followed by elution with 500ml ether:hexane (1:4) solvent mixture; followed by elution with 850 mlether:hexane (1:3) solvent mixture gives 6.2 g of3-thiobenzoyl-2,5-hexanedione, having the following analyses:

MS - Parent Ion, then decreasing order: 250, 105, 77, 43, 128, 106.

    NMR (CDCl.sub.3):                                                                             7.96 (d,1,J=2 Hz),                                                            7.88 (d,1,J=2 Hz),                                                            7.48 (m,3),                                                                   4.78 (q,1,J=5 Hz),                                                            3.06 (m,2),                                                                   2.29 (s,3),                                                                   2.14 (s,4) ppm                                                IR (KBr plate, thin film):                                                                     3060, 3000, 2960, 2910,                                                       1709, 1661, 1590, 1578,                                                       1445, 1355, 1204, 1172                                                        1154, 900, 759, 681, 640 cm.sup.-.sup.1                  

EXAMPLE VIII

The following formulation is prepared:

    Ingredient             Parts by Weight                                        ______________________________________                                        Liquid hydrolyzed vegetable                                                                          90.00                                                  protein                                                                       4-Methyl-5-beta-hydroxy-ethyl thiazole                                                               5.00                                                   Tetrahydro thiophene-3-one                                                                           1.00                                                   Furfuryl mercaptan     0.01                                                   2-nonenal              0.50                                                   Difurfuryl disulfide   0.49                                                   Dimethyl sulfide       0.50                                                   Methyl mercaptan       0.50                                                   3-Thioacetyl-2,5-hexanedione                                                                         2.00                                                   ______________________________________                                    

The 3-thioacetyl-2,5-hexanedione imparts a roasted meat taste to theabove formula and ties in and rounds up the other meat-like chemicals inthe formula. When 3-thioacetyl-2,5-hexanedione is replaced by3-thiobenzoyl-2,5-hexanedione, a similar effect is imparted to theover-all flavor and aroma pattern of the above formula.

EXAMPLE IX (PREPARATION OF 3-THIOISOVALERYL-2,5-HEXANEDIONE)

In a 250 ml three-necked flask fitted with magnetic stirrer, refluxcondenser and addition funnel are placed 10 g (0.068 moles) of3-mercapto-2,5-hexanedione, 5.4 g (0.068 moles) pyridine and 150 mlanhydrous diethyl ether. To this is added 8.3 g (0.068 moles) ofisovaleryl chloride during a four minute period. The resulting ethersolution is then washed, in sequence, with 150 ml of water, 50 ml of 4%HCl, 50 ml of saturated NaHCO₃ solution and dried over anhydrous sodiumsulfate. Sovent removal in vacuo gives 13.2 g crude 3-thioisovaleryl2,5-hexanedione.

Distillation of the crude gives 10.8 g product boiling at 108°-110°C at0.8-0.9 mm Hg pressure and having the following analyses:

Mass Spectral Analysis - In decreasing order (no parent ion): 43, 57,85, 128.

NMR Spectrum (CDCl₃)

           4.60         (q,1)                                                            2.95         (m,5)                                                            2.32         (s,3)                                                            2.17         (s,3)                                                            0.99         (d,6) ppm                                             

EXAMPLE X (PREPARATION OF 2-PROPYL-3-THIOACETYL FURAN) A. Preparation of2-propyl-2,5-dimethoxy-2,5-dihydro furan from 2-propyl furan

Reaction: ##SPC17##

Into a 500 ml three-necked flask equipped with mechanical stirrer,calcium carbonate drying tube and thermometer, the following materialsare placed:

    (i)      2-Propyl furan   25.0 g                                                                        (0.227 moles)                                       (ii)     Methanol, absolute                                                                             180 ml                                              (iii)    Sodium carbonate 47.1 g                                                                        (0.454 moles)                                   

The reaction mass is cooled to -10°C using a dry-ice acetone bath. Overa period of 20 minutes, a solution of 36.3 grams of bromine in 70 mlabsolute methanol is added dropwise while maintaining the reaction massat -12°C to -13°C. After the addition of the bromine solution, thereaction mass is stirred for 1.5 hours while maintaining same at -10°C.

The reaction mass is then mixed with 450 ml of saturated sodium chloridesolution. The resulting mixture is suction filtered and the filter cakeis washed with 100 ml of methylene dichloride. The resultant filtrateand washings are placed in a separatory funnel and the lower organicphase is drawn off. The aqueous phase is extracted with two 100 mlportions of methylene dichloride and the organic solutions are combined.The organic solution is then dried over anhydrous sodium sulfate andfiltered; and then concentrated in vacuo to a yellow liquid weighing32.7 grams. The major peak of this material determined by GLC contains2-propyl-2,5-dimethoxy-2,5-dihydro furan (GLC conditions: F & M 5750; 8feet × 1/4 inch SE-30; programmed from 130°-225°C at 4°C per minute,with an He flow rate of 80 ml/minute, chart speed 0.25 inch per minute).

B. Preparation of 4-oxo-2-heptenal

Reaction: ##SPC18##

Into a 250 ml three-necked reaction flask equipped with mechanicalstirrer and thermometer the following materials are added:

    (i)    2-Propyl-2,5-dimethoxy                                                                             32.7 g                                                   2,5-dihydrofuran prepared                                                                          (0.16 moles)                                             according to the process                                                      of Part A                                                              (ii)   Water (distilled)    325 ml                                        

The reaction mass is stirred for a period of 4 hours at 24°C. At the endof this period of time, the reaction mass exists in two phases; anaqueous upper phase and an organic lower phase. The aqueous upper phaseis decanted and placed in a 1 liter vessel for the following reaction C.

C. Reaction of 4-oxo-heptenal with thioacetic acid ##SPC19##

To the stirred aqueous solution produced in Part B, supra, of4-oxo-2-heptenal is added 0.4 ml piperidine. After the piperidineaddition, 12.4 grams of thioacetic acid is added to the reaction massover a period of 4 minutes while maintaining the reaction mass at atemperature in the range of 27°-32°C. After the thioacetic acid additionis complete, the reaction mass is stirred for 1.5 hours. The reactionmass is then placed in a separatory funnel and extracted with 100 ml ofmethylene dichloride. The methylene dichloride solution is thenseparated, dried over anhydrous sodium sulfate and concentrated to anorange oil weighing 23.8 grams. This orange oil is analyzed using GLC,NMR and IR analyses and determined to be substantially3-thioacetyl-4-oxo-heptenal-1.

Mass Spectral Analysis:

Molecular Ion, then in decreasing intensity: 202, 43, 28, 71, 55, 41,97, 83 m/e.

D. Preparation of 2-propyl-3-thioacetyl furan

Reaction: ##SPC20##

Into a 500 ml flask, equipped with reflux condenser, calcium chloridedrying tube, mechanical stirrer, thermometer and addition funnel, thefollowing materials are placed:

    (i)     Isopropenyl acetate   175 ml                                          (ii)    Concentrated sulfuric acid                                                                          0.5 ml                                      

The mass is heated to reflux (93°C) and, over a period of 20 minutes,while maintaining the reaction mass temperature at 91°-93°C, a solutionof 23.0 grams of the reaction product of Part C in 25 ml of isopropenylacetate is added from the addition funnel to the reaction mass withstirring. The reaction mass is then stirred and maintained at 91°C for aperiod of 30 minutes at which point 5.0 grams of sodium bicarbonate isadded to the mass.

The isopropenyl acetate cyclization agent is then distilled off at a pottemperature of 80°C and a head temperature of 50°C at 60 mm Hg pressure.The resulting residue is admixed with 50 ml benzene and 50 ml water. Theresulting mixture is placed into a separatory funnel and the layers areseparated. The benzene layer is filtered through anhydrous sodiumsulfate and is then concentrated in vacuo to a brown liquid weighing 5.0grams. This liquid is distilled through a short path microdistillationapparatus at 100°-103°C and 0.3 mm Hg pressure, yielding2-propyl-3-thioacetylfuran as confirmed by mass spectral and NMRanalyses.

Mass Spectral Analysis:

Molecular Ion, then in decreasing intensity: 184, 113, 43, 142, 27, 184.

                  NMR Analysis (CDCl.sub.3)                                       ______________________________________                                               Signal     Interpretation                                              ______________________________________                                        δ1.01 (t,3)                                                                            CH.sub.2 CH.sub.3                                              1.65 (m,2)     CH.sub.2 CH.sub.2 CH.sub.3                                                    O                                                                             ∥                                                     2.36 (s,3)     --C--CH.sub.3                                                  2.59 (t,2)     CH.sub.2 --CH.sub.2                                            6.32 (d,1)                                                                    7.35 ppm (d,1)                                                                ______________________________________                                    

What is claimed is:
 1. A process for producing a substituted orunsubstituted 3-thia alkane-4-one-1-al comprising the step of intimatelyadmixing an alk-2-ene-4-one-1-al having the structure: ##SPC21##with asulfur compound having the formula

    R.sub.3 SH

in the presence of an organic base selected from the group consisting ofsecondary amines and tertiary amines thereby providing a substituted orunsubstituted 3-thia alkane-4-one-1-al having the structure: ##SPC22##wherein R₃ is selected from the group consisting of acetyl and benzoyl;wherein R₂ is lower alkyl; and wherein R₄ and R₆ are the same ordifferent and are each selected from the group consisting of hydrogenand lower alkyl.
 2. The process of claim 1 wherein the organic base isselected from the group consisting of piperidine, pyridine, triethylamine, quinoline and alpha-picoline.
 3. The process of claim 1 whereinR₆ is hydrogen and R₂ is methyl.
 4. The process of claim 3 wherein R₃ isbenzoyl.
 5. The process of claim 3 wherein R₃ is acetyl.
 6. The processof claim 3 wherein R₄ is hydrogen.
 7. The process of claim 3 wherein R₄and R₆ are each hydrogen; R₂ is methyl.